P-Stim/ NSS: A Non Narcotic Alternative

for Acute and Chronic

Pain, Opioid Reduction and Sleep

Enhancement

Christopher R. Brown DDS, MPS

drchrisbrown@pstimus.com

Director of Medical Resources

Innovative Health Solutions

April 13, 2013

The clinical application and efficacy of percutaneous electrical neural

stimulation has been accepted throughout the physician community (1), has

been verified for use in many acute and chronic pain conditions (2) and also

been reported as an analgesic complementary therapy for the management of

pain secondary to bony metastasis (3). Percutaneous electrical neural stimulation is an entity unto itself and is

clearly distinguished from manual acupuncture, electrical acupuncture and/

or TENS. ( 4, 5 ) P-Stim / NSS neurostimulation therapy is further

distinguished as a separate entity from that of PENS.

Electro-acupuncture The NIH 1997 consensus conference supports the use of electro-acupuncture

for adult pos-operative and chemotherapy nausea, vomiting, and nausea for

pregnancy, postoperative dental pain, menstrual cramps, tennis elbow, and

addiction, stroke rehabilitation, carpel tunnel syndrome, headache, and

fibromyalgia (6). Although the complete mechanisms of actions are not fully understood

indications are that multiple biological responses are mediated by sensory

neurons within the central nervous system. These lead to activation of

pathways affecting systems in the brain and the periphery. Evidence

suggests that endogenous opioid peptides are released and produce analgesic

affects. Reduction of sympathetic stimulation of the hypothalamus and

pituitary glands, rich in sympathetic fibers, results in a broad cascade of

systemic alteration in the secretion of neuro-transmitters and neuro-

hormones helping cause change in blood flow both centrally and

peripherally. There is also evidence of alteration of immune functions. (7)

The theory and placement of acupuncture needles, both manual and

electrical, are based upon specific points (which vary according to which

variation/philosophy of acupuncture is referenced ) altering chi, energy flow,

reflex points , and flow of heat/cold.

TENS

TENS ( Transcutaneous Electricral- Neural Stimulation ) is designed to

deliver sufficient electrical stimulation via surface electrodes so that the

current density produced by the electrical field is able to excite the afferent

fibers in an adjacent nerve. (8) Surface electrodes are attached to the outer

skin and conductivity is enhanced by using a conducting gel. Different skin

and underlying tissues produces a non- homogeneous impedance resulting in

an unpredictable application of the electrical charge. By definition TENS is

transcutaneous rather than percutaneous or implanted.

PENS

Although there is a clear delineation between percutaneous electrical neural

stimulation and electro-acupuncture the physiological results may be similar

(9)

As opposed to acupuncture, the location of PENS needles is determined by

neurological and vascular proximity within a sclerodermal, myodermal or

dermatological distribution rather than theories of energy flow or reflex

points. ( 10,11) Percutaneous electrical neural stimulation therefore provides

in-direct stimulation to the nerves( 12) via a battery-operated pulse generator

which delivers current that can be varied in form, intensity, frequency, and is differentiated by the use of fine needles inserted through the skin to stimulate peripheral sensory nerves ( 13 ) The PENS needles are always placed in the proximity of the pain for indirect stimulation.

P-STIM / NSS

The P-Stim/NSS neurostilulator is programmed to provide a stimulation

comprised of 1 HZ , 1 ms monophasic impulses in a rectangular wave form,

with the current inverted every second pulse, changing polarity ( to avoid

polarizing effects) , with an amplitude of 4 V. ( 14 )The auricular

implantation of the P-Stim/NSS neurostimulator is via an electrode / needle

array as opposed to only needles as found in all other percutaneous electrical

techniques. The electrode/needle array is implanted according to

verifications of the individuals arterial and cranial nerve anatomy.

TENS interrupts peripheral transmission as described in the gate-control

theory ( 15 ) , therefore producing local analgesia while the percutaneous

implantation of the electrode/needle array of the P-Stim/NSS

neurostimulator directly into the auricular neurovascular complexes acts at

the midbrain and spinal cord affecting descending and ascending inhibition

and neuro-matrix alteration.

In general the use of PENS is often more effective then TENS as it bypasses

skin resistance and delivers electrical stimulation in closer proximity to the

nerve endings and soft tissues surrounding the nerves. (16). It has also been

found to be more effective for chronic low back pain than TENS (17)

( see Table A for comparisons )

Clinical Application of the P-Stim/NSS Neurostimulator for

the treatment of Acute and Chronic Pain The P-Stim/NSS neurostimulator is the only ambulatory, physician applied,

minimally invasive application of electrical neural stimulation implanted

directly into the neurovascular bundles of the external ear verified by

transillumination co-joined with skin impedance measurement. A generator

located behind the affected ear, produces electrical stimulation impulses

which are transferred via an electrode/ needle array to branches of cranial

and/or occipital nerves and sympathetic fibers of the arterial branches. The P

Stim/NSS neurostimulator allows for continuous, intermittent neural stimulation for up to four days while allowing the patient to remain

ambulatory during the treatment of both acute and chronic pain. (18 )

Electrode implantation into the skin of the ear allows for direct access to

branches of Cranial Nerves V, VII, IX, X (19) as well as branches of the

occipital nerves.(20) Direct access to the arterial branches of the head and

neck are accessible (21) and reduction of sympathetic stimulation results in

an increase of vascular flow rate, reduction of vascular resistance, and increase of perfusion (22, 23 ) The arterial branches of the superficial

temporal artery ( STA ) and the posterior auricular artery ( PAA ) form a

rich interconnecting complex network the terminal branches of which

anastomose though out the ear.( 24 )

( Table B )

The device is thought to alter production and utilization of serotonin via

vagal (CN X) stimulation, and meningeo-vascular dilation secondary to

decreased sympathetic (or increased parsympathetic ) tone. ( 25, 26,27, 28,

29 ) Since the external auricle is rich with branches of cranial nerves V,VII, IX,

and X , branches of the lesser and greater occipital nerves, the upper cervical

plexus and arterial branches (STA, PAA ) that directly lead into the head and

neck, the P-Stim/NSS neurostimulator provides direct stimulation to these

entities and directly affects the anatomical areas through which they

traverse. ( 30 , 31 ) Sensory innervation found in the external auditory

meatus can reflect or refer pain from the ear, upper and lower digestive

tracts, TMJs, teeth, salivary glands, and / or the thyroid gland.( 32 ) The trigeminal nerve also accompanies the superficial temporal artery and vein

which directly feeds into the TMJs ( 33 ) There is not an anatomical area which is solely one type of cranial nerve or

arterial branches at any given location in an area of the external ear. ( 34 ) .

Innervation of the external ear is diverse and may vary from individual to

individual ( 35 ) Each zone of the external ear is innervated by two different cranial branches of the lesser and greater occipital nerves and upper cervical plexus

, and various arterial branches which lead to the head and neck. There is no

part of the ear however which contains three different cranial nerve branches

( 36 ) Many of the pathways intersect and interact in the trigeminal complex.

Anti-nociceptive activity in the trigeminal complex involves inhibitory

control of afferent nociception, serotonin fluctuation and concurrent vagal

stimulation. The trigeminal complex is an essential component in the

development of central sensitization and peripheral sensitization probably

through sympatho-afferent coupling, a key to sympathetic pain maintenance

( 37 ) The mandibular division of Cranial nerve V ( trigeminal ) is also

implicated with mediation of migraine headaches. Direct implantation into

branches of the trigeminal nerves can be found in the lobe, inner concha and

anterior to the tragus of the ear. Stimulation of these areas can also have a

positive effect on cervical pain ( 38 ) Branches of the vagal nerve are found in almost all aspects of the external

ear. There are some regions with a greater concentration than others but all

are easily accessed with the leads of the P-Stim/NSS neurostimulator. The

Vagus nerve ( X ) carries sensory innervation from the lower digestive tract through the mucosa of the valleculae, piriform sinuses, larynx and internal

branch of the laryngeal nerve. ( 39 ) Several physiological mechanisms

have been linked to vagal excessive sympathetic stimulation including

cardiovascular disease, heart rate variability, cancer, Alzheimers disease, and metabolic syndrome. The commonality of these disorders are

inflammatory reactions mediated by excessive sympathetic responses which

are inhibited by the vagal nerve along its extensive tract. ( 40) . Long term

eating behavior can be affected as well by the vagus nerve by transmitting

signals from the upper gut to the hypothalamus ( 41 ) Direct stimulation of the cranial nerves and arterial branches by the P-

Stim/NSS neurostimulator directly affects the mid brain and specific

neurological tracts into the spine by modulating the level of central

sensitization by altering the strength of the descending anti-nociceptive

signal generated in the trigeminal complex altering serotonin production and utilization, regulating dysautonomia, producing a marked decrease in the

VAS (visual analog scale) of pain (42. ) The P-Stim/NSS neurostimulator has been shown to affect a change in heart rate variability, increase in blood

perfusion, increase in vascular flow rate , increase in endorphin production,

reduction of vascular resistance, decrease in sympathetic stimulation and an

increase in parasympathetic function. (43) Reduction of repetitive noxious

stimuli via the use of the P-Stim/NSS neurostimulator over a period of time

can reduce temporal summation and help alleviate a central spine

mechanism known as wind up indicated in Central Sensitization Syndrome.( CSS) (44 ) The mechanism of induced analgesia is speculated

to be as a result of neuro-modulation ( inhibition of small C fibers ) ( 45) and

an increase of endogenous morphine - like substances within the central

nervous system ( CNS) ( 46 ) The P-Stim/NSS neurostimulator achieves a

rapid onset of analgesia and is a safe, additive , non addictive, non

pharmaceutical approach to pain management in a clinical setting ( 47 ) The P-Stim/NSS neurostimulator is also found to alleviate other symptoms

commonly associated with CSS which involves hyper-excitability of the CNS resulting in headaches, body pain, confusion, sleep disturbances, and

chronic fatigue ( 48 ) . Direct access by the P- Stim/NSS neurostimulator

into the spinal cord via the lesser and greater occipital nerves, cranial nerves,

and sympathetic reduction at the mid brain along with endogenous

endorphin production, may account for the reduction of these symptoms.

Electro-analgesia is thought also to be mediated by three types of CNS

opioid receptor sites : mu, sigma, and kappa ( 49 ) producing a more

regionalized analgesia effect commonly found with the use of the P-

Stim/NSS neurostimulator.

The decrease in the use of oral analgesics including opioids has been noted

as well with the P-Stim/NSS neurostimulator. ( 50, 51) All symptom

reduction and behavioral changes noted in the APS Bulletin and University

of Birmingham review correlate well with those found with the P-Stim/NSS

neurostimulator ( 52, 53 ).

The use of the P-Stim/NSS neurostimulator has consistently indicated an

increase in sleep quality ( 54 ) and has suggested indications for use in

Peripheral Arterial Occlusion Disease (55) Other percutaneous electrical neural stimulation methods stimulate in only

15, 30-45 minute applications applied twice per week over the course of

several weeks. An increase in analgesia was noted by the longer duration

of various applications ( 56 ) All noted percutaneous electrical neural

stimulation techniques are designed to follow dermatomes ( 57 ) while the

P-Stim/NSS neurostimulator directly implants into the cranial nerves, blood

vessels, and the soft tissue surrounding them. Auricular neurovascular

bundles/ arterial branches are initially visualized by transillumination

utilizing an Auricular Transilluminator ( IHS, Versailles, IN ) via a specific

technique. Electrical impedance of the auricular skin is then measured by the

use of an Ohm meter ( Multi-Point Stylus-Biegler corp , Vienna Austria )

via a specific technique. Utilization of both techniques is essential to help

verify the most optimal electrode implantation into the underlying

neurovascular bundles. The positive results achieved by the stimulation is

dependent on the precise placement of the electrode into the neurovascular

bundles. ( 58 )The precise neurovascular application and clinical technique,

including transillumiation clearly separates the use of the P-stim/NSS

neurostimulator from acupuncture, electro-acupuncture,TENS, and PENS.

The inclusion of both techniques to locate and place the electrode complex

directly into the neurovascular bundles is a technical advancement of

previously published methodology, experimental approach, and rationale. ( 59 )

The P-Stim/NSS neurostimulator is programmed to run for three hours on

and three hours off for a four day cycle to reduce the risk of adaptation or

tolerance. Accepted clinical protocol is to use three devices in a row over a

period of twelve days, with no break, followed by another device after seven

days of no treatment. When a residual reduction in symptoms ( reduction

lasting longer than the life of the P-Stim/NSS neurostimulator as verified by

patient history and VAS scale ) is found there is an extension of non

treatment time between each application. The symptom reduction is often

cumulative and residual. The majority of patients may require 6-9 devices to reach quiescence. In acute situations such as surgical procedures a pre-

treatment and post treatment use of the devices ( 2 total) to reduce

sympathetic stimulation and increase endorphin production is suggested to

minimize post operative pain, edema, and swelling. Contraindications for P-

Stim/NSS neurostimulator use are chronically low blood pressure, recent

organ transplants, any type of electric heart or brain device, history of

seizures, blood thinners, or pregnancy. The reduction in symptoms of such systemic disorders such as fibromyalgia,

knee pain, lower back pain, inflammation, edema/ ischemia are thought to

be from the effect on the mid brain , endorphin production, and stimulation

of spinal and peripheral inhibitory pain mechanisms via direct neurovascular

stimulation and reduction of sympathetic fibers in the arterial walls. The P-

Stim/NSS neurostimulation system allows for direct, physician applied,

ambulatory, continual treatment. The use of electrical stimulation as well as the P-Stim/NSS neurostimulator

has reduced the need for analgesic drugs such as NSAIDS, and central

acting Opioids . (60)This may also help alleviate the dependencies,

addictions, and other commonly complications found with opioid use such

as immunosupression , constipation, and hyperalgesia. (61, 62, 63, 64) Reduction of pain and the reduced use of opioids may reduce the length of

post operative hospital stays therefore reducing the chance of HAIs ( hospital acquired infections ) ( 65 ) The electrical neural stimulation such as

the P- stim/NSS neurostimulator can be considered as a useful, non

pharmaceutical adjunct or replacement for opioid and non opioid analgesics

and should be considered as a viable non narcotic treatment option for

chronic pain with sleep disturbance co-morbidity. ( 66 )

The APS bulletin (vol 9, Number 2, March/April 1999 White, MD PhD ,

Phillips, et al ) compared findings from a group of publications ( 67 ) as well

as did The University of Birmingham, Alabama. ( 68 ) and collectively noted the following results consistently with peripheral neural stimulation:

1. A reduction in VAS and other pain scores compared to sham needle

placement and placebo in tension, migraine, and post traumatic headache (

69 )

2. Decrease in frequency of Sciatica pain (70 ) 3. Decrease post herpetic and diabetic neuralgia (71) 3. A decrease in the use of oral analgesics ( both opioid and non opioid ) 4. An increase in physical activity 5. Improvement quality of sleep. (72,73 )

Summary :

The use of percutaneous electrical neural stimulation is a non narcotic

alternative to acute and chronic pain.. The P-Stim/ NSS neurostimulator , is

the only physician applied ambulatory , continuous, home based therapy

which is designed to be directly implanted into auricular neural vascular

bundles ascertained by auricular transillumination and impedance

measurement of the neuro-vascular anatomy. The use of the P-Stim/NSS

neurostimulator also substantially reduces the need for analgesics including

NSAIDs and central acting opioids reducing the co-morbidities of unwanted significant sided effects often associated with analgesic pain control such as

renal impairment, cerebral vascular accidents, heart failure, gastrointestinal

bleeding, delirium, and potential for slip and fall with resulting hip fractures.

( 74, 75 ) The use of percutaneous electrical neural stimulation has been shown as a

viable alternative to escalating opioid and non opioid dosages even in the

management of cancer pain. ( 76, 77 , 78 , 79 )

The P-Stim/NSS neurostimulator is an easily applied, cost effective , safe ,

non pharmaceutical treatment alternative reducing ancillary health care costs

associated with acute and chronic pain , sleep, opioid use, and peripheral

arterial occlusion disease. Through the reduction of pain, sympathetic

responses and opioid consumption with associated potential

immunosuppression , the immediate post operative use of the P-Stim/NSS

neurostimulator may reduce healing time , hospital length of stay and

therefore reducing the risks of HAIs ( healthcare acquired infections ). Clinical indications for the use of P-Stim/NSS neurostimulator are the

following:

Chronic:

1. Musculoskelatal pain

2. Fibromyalgia 3. Headache ( tension, migraine, non migraine) 4. Neuralgias ( sciatica, Trigeminal neuralgia, greater and lesser occipital ) 5. Arthralgia ( Knee, back, TMJ ) 6. Pain associated with cancer 7. Co-morbid anxiety/depression 8. Low back pain 9. Neck pain 10. Inflammatory reactions secondary to chronic conditions 11. Diabetic neuropathy 12. Tinnitus 13. Sleep disturbances Acute : 1. Musculoskelatal pain 2. Headache ( tension, migraine, non migraine) 3. Arthralgia ( Knee, back, TMJ ) 4. Pre and post surgical procedures 5. Localized Swelling 6. Spinal inflammatory disc disorders

Because of the longer length of application of the P-Stim/NSS

neurostimulator both actively ( three hours) and duration ( four days ), a

longer residual effect as a result of neuroplastic changes and endogenous

endorphin production has been found beyond that of other electrical neural

stimulation techniques. The use of the P-Stim/NSS neurostimulator as an adjunct with other means

of treatment such as oral medications, injectables, surgical procedures,

physical and manipulative therapy, exercise, and nutrition, integrates well

into the established medical model. Use in out- patient and hospital post

operative acute situations holds great promise for reduced healing time, pain

control, reduction of opioid consumption, reduced hospital stays, and along

with good infection control techniques, a reduction in healthcare acquired

infections.

I wish to thank Dr. Art Roberts, DDS, MD, MSc for his contributions to this publication

TABLE A P-Stim Acupuncture Electro- Accupuncture TENS PENS ___________________________________________________________ Use of a generator X X

___________________________________________________________________________________

Percutaneous X X X X

___________________________________________________________________________________

Uses percutaneous

electrode/needle complex X

___________________________________________________________________________________

Placement determination

A. Predetermined

points in a manual X X

___________________________________________________________________________________

B. According to tradition X X

___________________________________________________________________________________

C. Based upon various

Life flow/chi X X

___________________________________________________________________________________

D. Reflex points X X

___________________________________________________________________________________

E. At area of discomfort X X X X

___________________________________________________________________________________

F. Dermatomes X X

___________________________________________________________________________________

G. Visualization of

neurovasvular bundles X

___________________________________________________________________________________

H. Measure of skin

impedance X * *

___________________________________________________________________________________

I. Cranial neuro-vascular

bundles X

___________________________________________________________________________________

Ambulatory / home based

Care X X

___________________________________________________________________________________

Continuous stimulation

Over several days X * X

___________________________________________________________________________________

Physician applied X ** ** X

___________________________________________________________________________________

Research verification

of effectiveness X X X X X

___________________________________________________________________________________

* Option ** State by state licensing requirements for acupuncture

Vascularization of the Auricle Photos from Tillotta, Lazaroo, et al

Surg Radiol Anat ( 2009 ) 31: 259-265

Table B

Arterial network from the superficial temporal artery ( STA ) and the Posterior Auricular Artery (PAA )

Branches of the PAA

( medial aspect of the auricle )

PAA branches of the lateral aspect of the ear

Footnotes:

1. Anthem Clinical UM Guidelines, Electrical Nerve Stimulation,

Transcutaneous, Percutaneous.Guideline # CG-DME-04, Status: revised.

Current effective date: 10/12/2011. Last review date: 8/18/2011. 2. Blue Cross of Idaho. MP 7.01.29. Percutaneous Electrical Nerve

Stimulation ( PENS) and Percutraneous Neuromodulation Therapy ( PNT).

Medical Policy. Section Surgery issue 8/20/11 Original Policy date

11/30/96. Last literature search 8/20/11 3. Ahmed, Hersham M.D., Craig, William M.D., et al. Percutaneous

Electrical Nerve Stimulation ( PENS): A Complementary Therapy for the

Management of Pain Secondary to Bony Metastasis. Clinical Journal of

Pain. Dec 1998, vol 14 issue 4, pp 320-323. 4. Blue Cross/ Blue Shield Protocol . Percutaneous Electrical Nerve

Stimulation ( PENS ) or Percutaneous Neuromodulation Therapy ( PNT ) (

70129 ) effective October 1, 2009. Literature review May 2010. 5. University of Birmingham ARIF ( Aggressive Research Intelligence

Facility. ARIF Request. Percutaneous Electrical Stimulation ( PENS)

Chronic Pain ( Breast and Back ) Pain. Jan 2007. 6. Wilentz MA. NIH Consensus Development Conference on Acupuncture,

APS Bulletin, Vol 8,no 2,1998 7. Wilentz MA. Ibid. 8. Wall P, Melzack R. Textbook of Pain. Churchill Livingston. Edinburg,

London, Melbourne, New York, 1984.pp 680-689. 9. Sabine M, Sator-Katzenschlager MD, Seles Jozef MD. Electrical

Stimulation of Auricular Acupuncture Points is More Effective than

Conventional Manual Auricular Acupuncture in Chronic Cervical Pain: A

Pilot Study. Anesth Analog, 2003; 97:1469-1473. 10. Blue Cross/ Shield Protocol. Percutaneous Electrical Nerve Stimulation

( PENS ) or Percutaneous Neuromodulation Therapy ( PNT ) ( 70129 )

effective October 1, 2009. Literature review May 2010. 11. Oleson T PhD, Medical Acupuncture, A Journal for Physicians By

Physicians. Fall 1999/ Winter 2000, Vol 11, no 2 12. Johnson Michael, Martinson Melissa. Efficacy of Electrical Nerve

Stimulation for Chronic Musculoskeletal Pain: A Meta-Analysis of

Randomized Controlled Trials. Pain130 ( 2007 ) pp 157-165. 13. Blue Cross Blue Shield of Delaware. Medical Policy Reference Manual.

Medical Policy. Policy Number 7.01.Z-7 Archived 12/1/2011. Policy Title Electrical Nerve Stimulation. Original

MPC Approval 10/11/11. 14 . Kaniusas Eugenijus, Szeles Jozsef, Varoneckas Giedrius. Adaptive

Auricular Electrical Stimulation Controlled by Vital Biosignals. Biodevices

Second Internaltional Connference on Biomedical Elecronics and Devices

Proceedings. Portugal Jan 14-17, 2009.pp 304-309. 15. Wall P, Melzack R. Textbook of Pain. Churchill Livingston. Edinburg,

London, Melbourne, New York, 1984.pp 680-689. 16. White Paul, Phillips Jennifer, et al. Percutaneous Electrical Nerve

Stimulation ( PENS ): A Promising Alternative-Medicine Approach to Pain

Management. Library APS Bulletin vol. 9, no. 2, March/April 1999. 17. Yokohama M MD, Sun Xiaohul MD, et al. Comparison of Percutaneous

Electrical Nerve Stimulation with Transcutaneous Electrical Nerve

Stimulation for Long-Term Pain Relief in Patients with Chronic Low Back

Pain. Anestyhesia and Analgesia, June 2004, vol. 98 no 6, pp 1552-1556. 18. Sabine M, Sator-Katzenschlager MD, Seles Jozef MD. Electrical

Stimulation of Auricular Acupuncture Points is More Effective than

Conventional Manual Auricular Acupuncture in Chronic Cervical Pain: A

Pilot Study. Anesth Analog, 2003; 97:1469-1473.

19. Weissman Jane. A Pain in the Ear: The Radiology of Otalgia. AJNR 18.

Oct 1997 pp 1641-1651. 20. Peuker Elmer, Filler Timm. The Nerve Supply of the Human Auricle.

Clinical Anatomy. 15, 2002. pp 35-37. 21. Weissman Jane. A Pain in the Ear: The Radiology of Otalgia. AJNR 18.

Oct 1997 pp 1641-1651. 22. Long Jennifer, Jay Steven, et al. Veg-A and Semaphprin 3A: Modulators

of Vascular Sympathetic Innervation. Dev Biology. 2009 Oct 1; 334 ( 1 ) pp

119-132. 23. Kaniusas Eugenijus, Szeles Jozsef, Varoneckas Giedrius. Adaptive

Auricular Electrical Stimulation Controlled by Vital Biosignals. Biodevices

Second Internaltional Connference on Biomedical Elecronics and Devices

Proceedings. Portugal Jan 14-17, 2009.pp 304-309.

24. Tilotta F, Lazaroo, et al.A Study of the Vascularization of the Auricle by

Dissection and Diaphanization. Surg Radiol Anat ( 2009) 31:259-265

25.Schlaepfer TE, Frick C, Zobel A, et al, Vagus nerve stimulation for

depression: efficacy and safety in a European study. Psychol Med, 2008.

38(5): p. 651-661.

26. Zhang Y, Popovic ZB, Bibevesky S, et al, Chronic vagus stimulation

improves autonomic control and attenuates systemic inflammation and heart

failure progression in a canine high-rate pacing model. Circ Heart Fail,

2009. 2(6): p. 692-699

27.Multon S, Schoenen J, Pain control by vagus nerve stimulation: from

animal to man.. and back Acta neurol belg, 2005(105): p. 62-67

28. La Marca R, Nedeljkovic M, Yuan L, Maercker A, Ehlert U, Effects of

Auricular Electrostimulation on Vagal Activity in Healthy Men: Evidence

from a Three Armed Randomized Trial. Clin Sci, 2010. 118: p. 537-546.

29.George MS, N.Z., Borckardt JJ, Anderson B, Foust MJ, Burns C,Kose S,

Short EB, Vagus nerve stimulation for the treatment of depression and other

neuropsychiatric disorders. Exp Rev Neurotherapeutics, 2007. 7(1): p. 1-12

30. Peuker Elmer, Filler Tim. The Nerve Supply of the Human Auricle.

Clinical Anatomy. 15, 2002. pp 35-37. 31. Weissman Jane. A Pain in the Ear: The Radiology of Otalgia. AJNR 18.

Oct 1997 pp 1641-1651. 32.Weissman Jane. Ibid 33. Weissman Jane. Ibid 34. Peuker Elmer, Filler Timm. The Nerve Supply of the Human Auricle.

Clinical Anatomy. 15, 2002. pp 35-37. 35. Hollinshead WH. Anatomy for Surgeons, vol 1: The Head and Neck.

New York, NY: Harper and Row; 1968. 36. Peuker Elmer, Filler Timm. The Nerve Supply of the Human Auricle.

Clinical Anatomy. 15, 2002. pp 35-37. 37. Roberts Arthur. Central Sensitization: Clinical Implications for Chronic

head and Neck Pain. Clinical Medicine and Diagnostics; 2011; 1 ( 1 ): pp 1-

7. 38. Sator-Katzenschlager SM, Szeles JC, et al.Electrical Stimulation of

Auricular Acupuncture Points is More Effective than Conventional Manual

Auricular Acupuncture in Chronic Cervical Pain: a Pilot Study. Anesth

Analg. 2003 Nov; 97(5): 1469-73

39. Weissman Jane. A Pain in the Ear: The Radiology of Otalgia. AJNR 18.

Oct 1997 pp 1641-1651. 40. DeCouck M, et al. You May Need the Vagus Nerve to Understand

Pathophysiology and to Treat Diseases.. Clin Sci . 122( 7 ) ( Lond ). April

2012; pp 323-328 . 41. Chung, Owyano, Heldsinger Andrea. Vagal Control of Satiety and

Hormonla Regulation of Appetite. J Neurogastroenterol Motil vo. 17 ( 4 )

Oct 2011 pp 338-348 )

42. Szeles Jozef MD, Litscher Gerhard. Objectivation of Cerebral Effects

with a New Continuous Electrical Auricular Stimulation Technique for Pain

Management. Neurological Research, 2004. Vol 26 October 2004. pp 797-

800. 43. Sabine M, Sator-Katzenschlager MD, Seles Jozef MD. Electrical

Stimulation of Auricular Acupuncture Points is More Effective than

Conventional Manual Auricular Acupuncture in Chronic Cervical Pain: A

Pilot Study. Anesth Analog, 2003; 97:1469-1473. 44. Meeus Mira, Nijs Jo. Central Sensitization: A Biopsychsocial

Explanation for Chronic Widespread Pain in Patients with Fibromyalgia and

Chronic Fatigue Syndrome. Clin Rheumatol ( 2007 ) 26. pp 465-473. 45. White P, MD, Fanza Wm MD, et al. Percutaneous Neuromodulation

Therapy: Does Location of the Electrical Stimulation Effect the Acute

Analgesia Response? Anesthesia and Analgesia, Oct 2000, vol 91, no 4 pp

949-954. 46. Hesham Ahmed MD, White Paul PhD. Use of Percutaneous Electrical

Nerve Stimulation ( PENS ) in the Short Term Management of Headache.

Headache 2000: 40: 311-315. 47. Sabine M, Sator-Katzenschlager eet al. Auricular Electro-Acupuncture

as an Additional Perioperative Analgesic Method During Oocyte Aspiration

in IVF Treatment. Oxford University Press. March 2006. pp 1-7. 48. Meeus Mira, Nijs Jo. Central Sensitization: A Biopsychsocial

Explanation for Chronic Widespread Pain in Patients with Fibromyalgia and

Chronic Fatigue Syndrome. Clin Rheumatol ( 2007 ) 26. pp 465-473. 49. Hesham Ahmed MD, White Paul PhD. Use of Percutaneous Electrical

Nerve Stimulation ( PENS ) in the Short Term Management of Headache.

Headache 2000: 40: 311-315. 50. Sabine M, Sator-Katzenschlager MD, Seles Jozef MD. Electrical

Stimulation of Auricular Acupuncture Points is More Effective than

Conventional Manual Auricular Acupuncture in Chronic Cervical Pain: A

Pilot Study. Anesth Analog, 2003; 97:1469-1473. 51. Szeles Jozef MD, Litscher Gerhard. Objectivation of Cerebral Effects

with a New Continuous Electrical Auricular Stimulation Technique for Pain

Management. Neurological Research, 2004. Vol 26 October 2004. pp 797-

800. 52. White Paul, Phillips Jennifer, et al. Percutaneous Electrical Nerve

Stimulation ( PENS ): A Promising Alternative-Medicine Approach to Pain

Management. Library APS Bulletin vol. 9, no. 2, March/April 1999. 53. University of Birmingham ARIF ( Aggressive Research Intelligence

Facility. ARIF Request. Percutaneous Electrical Stimulation ( PENS)

Chronic Pain ( Breast and Back ) Pain. Jan 2007

54. Kaniusas E, Szeles J., Varoneckas G. Adaptive Auricular Electrical

Stimulation Controlled by Vital Biosignals. Biodevices 2009 Second

International Confrence on Biomedical Electronics and Devices.

Prooceedings Portugal Jan 14-17 2009. p 304-309

55. Payrits T, Ernst A, et al.Vagal Stimulation- A New Possibility for

Conservative Teatment of Peripheral Arterial Occlusion Disease. Zentralbi

Chir 2011;136:431-435 56. Hamza M MD, Ghoname El-sayed MD. Effect of Duration of Electrical

Stimulation on the Analgesic Response in Patients with Low Back Pain.

Anesthesiology. Dec 1999 Vol 91 ( 6 ) p 1622-1639. 57. Weiner Debra, Perera Subashen, et al. Efficacy of Percutaneous

Electrical Nerve Stimulation and Therapeutic Exercise for Older Adults with

Chronic Low Back Pain: A Randomized Controlled Trial.Pain, 140 ( 2008 )

344-357.

58. Kaniusas E, Giedrius V, et al. Optic Visualization of Auricular Nerves

and Blood Vessels: Optimisation and Validation. IEEE Transactions on

Instrumentation and Measurement, Vol. 60, No 10, October 2011.

59. Kaniusas E, Gierdrius V, et al. Ibid

60. Sabine M, Sator-Katzenschlager MD,, Scharbert G MD. The Short-and

Long-Term Benefit in Chronic Low Back Pain Through Adjuvant Electrical

Versus Manual Auricular Acupuncture. Anesth Analog 2004: 98: 1359-64. 61.Wei Gang, Moss Jonathon, Yuan Chun-Su. Opioid Induced

Immunosuppression: Is it Centrally Mediated or Peripherally Mediated?

Biochemical Pharmacology 65 ( 2003 ) pp 1761-1766. 62. Berde Charles MD, PhD. Peripheral, Spinal and Supraspinal Targets of

Opioids and NSAIDs. International Association for the Study of Pain. Technical Corner from the IASP Newsletter My/June 1996. 63. Hay Justin, White Jason, Bochner, et al. Hyperalgesia in Opioid-

Managed Chronic Pain Opioid- Dependent Patients. The Journal of Pain,

Vol 10, No. 3 ( March ), 2009. pp 316-322. 64. Wei Gang, Moss Jonathon, Yuan Chun-Su. Opioid Induced

Immunosuppression: Is it Centrally Mediated or Peripherally Mediated?

Biochemical Pharmacology 65 ( 2003 ) pp 1761-1766. 65. Rubin Robert, Harrington Catherine, Poon Anna, et al. The Economic

Impact of Staphylococcus Aureus Infection in New York City Hospitals.

Emerging Infectious Diseases, Perspectives. Vol. 5 Jan-Feb 1999. pp 9-17. 66. Johnson Michael, Martinson Melissa. Efficacy of Electrical Nerve

Stimulation for Chronic Musculoskeletal Pain: A Meta-Analysis of

Randomized Controlled Trials. Pain. vol30 ( 2007 ) pp 157-165. 67. White Paul, Phillips Jennifer, et al. Percutaneous Electrical Nerve

Stimulation ( PENS ): A Promising Alternative-Medicine Approach to Pain

Management. Library APS Bulletin vol. 9, no. 2, March/April 1999 68. University of Birmingham ARIF ( Aggressive Research Intelligence

Facility. ARIF Request. Percutaneous Electrical Stimulation ( PENS)

Chronic Pain ( Breast and Back ) Pain. Jan 2007. 69. Ghoname El- sayed MD, Craig Wm. MD, et al. Use Of Percutaneous

Electrical Nerve Stimulation ( PENS) for Treating ECT-Induced Headaches.

Headache 1999; 39: 502-505.

70. Ghoname El-sayed, White Paul, et al. Percutaneous Electrical Nerve

Stimulation: An Alternative to TENS in the Management of Sciatica. Pin 83

( 1999) 193-199. 71. Hamza Mohamed MD, White Paul PhD. Percutaneous Electrical Nerve

Stimulation; A Novel Therapy for Diabetic Neuropathic Pain. Diabetes Care

23: 365-370, 2000. 72. White Paul, Phillips Jennifer, et al. Percutaneous Electrical Nerve

Stimulation ( PENS ): A Promising Alternative-Medicine Approach to Pain

Management. Library APS Bulletin vol. 9, no. 2, March/April 1999. 73. Ghoname El-sayed MD , Craig Wm MD, et al. The Effect of Stimulus

Frequency on the Analgesic Response tp Percutaneous Electrical Nerve

Stimulation in Pataients with Chronic Low Back Pain. Anesthesis and

Analgesia . April 1999, vol 88, no 4. pp 841-848. 74. Weiner Debra, Perera Subashen, et al. Efficacy of Percutaneous

Electrical Nerve Stimulation and Therapeutic Exercise for Older Adults with

Chronic Low Back Pain: A Randomized Controlled Trial. Pain, 140 ( 2008 )

344-357. 75. Weiner Debra, Ibid 76. Ahmed Hesham MD, Craig Wm MD. Percutaneous Electrical Nerve

Stimulation ( PENS): A Complementary Therapy for the Management of

Pain Secondary to Bony Metastasis. Clinical Journal of Pain. Dec 1998, vol

14, ( 4 ) .pp 320-232. 77. Ghoname El-sayed MD , Craig Wm MD, et al. The Effect of Stimulus

Frequency on the Analgesic Response tp Percutaneous Electrical Nerve

Stimulation in Patients with Chronic Low Back Pain. Anesthesis and

Analgesia . April 1999, vol 88, no 4. pp 841-848. 78. Ghoname El- sayed MD, Craig Wm. MD, et al. Use Of Percutaneous

Electrical Nerve Stimulation ( PENS) for Treating ECT-Induced Headaches.

Headache 1999; 39: 502-505.

79. Ghoname El-sayed MD, Craig MD, et al. Percutaneous Electrical Nerve

Stimulation for Low Back Pain. JAMA, March 3, vol 281, NO. 9. pp

818823.